Chemical Imbalance and Adrenal Fatigue Syndrome – Part 1

By: Michael Lam, MD, MPH; Justin Lam, ABAAHP, FMNM

Adrenal fatigue can even affect the firing of neurons and cause a chemical imbalanceNeurotransmitters (NTs) are chemicals in the brain that act as messengers, transmitting signals between the neurons, allowing communication to take place with the multitude of organ systems functioning within the body. These are potent neurochemicals that regulate nearly every function in the body including, physical and cognitive performance, weight, the perception and response to pain, sleep patterns and our emotional and mental state of being. A chemical imbalance in these will be felt everywhere in the body.

Scientific research reveals that malfunctions in neurotransmission, such as a chemical imbalance, deficiency, or disruption is very common these days and are the root cause of many commonly found health conditions. When our neurotransmitters experience a chemical imbalance or are not working at optimum levels our mind and body cannot communicate clearly and effectively. It is estimated that about 80 percent of people have some form of chemical imbalance in their neurotransmitters. Fortunately, only a small number are clinically symptomatic and debilitating.

Brain function will be affected whenever there is a chemical imbalance or a dysfunction of poorly functioning NTs or malfunctioning hormonal axis that are the ultimate conduit upon which NTs exert their effect, such as the hormonal hypothalamic-pituitary-adrenal axis (HPA). This paper will examine both defects in a setting of Adrenal Fatigue Syndrome.

Can a Chemical Imbalance Affect How our Nerves Communicate with Each Other?

Before we can fully comprehend the effect neurotransmitter problems can have on us, we first need to understand how they communicate with each other. We can compare our nervous system to the electrical system in our homes. Nerve cells communicate with each other via tiny circuits called neuronal pathways. What’s different is that our nerve cells don’t touch each other, they come close but there is a gap between them called a synaptic cleft. The neuron sending the message is the presynaptic cell or axon, and the neuron receiving the message is the postsynaptic cell, or dendrite.

The direction of communication is one-way and to assist the message to make it across the synapse from the presynaptic cell to the postsynaptic cell, chemicals called neurotransmitters are used. For example, a typical synaptic transmission using the neurotransmitter serotonin would involve a presynaptic cell producing serotonin from tryptophan (an amino acid), accumulating the serotonin into small vesicles, which are in the terminals at the end. When your brain sends a signal (an action potential) it goes down the presynaptic cell and arrives at the end terminals. Upon arrival, serotonin is released and fills the synaptic cleft, crosses, and binds with its serotonin receptors located on the surface of the postsynaptic cell. When there is adequate serotonin binding to its receptors, a certain minimum threshold level is attained, and the signal (action potential) will arrive in the cell and continue to be propagated by moving on to the next cell. The goal is for the signal to reach its intended target, like skeletal muscle fibers in order to cause movement.

Serotonin is an important neurotransmitter and a chemical imbalance can be impactfulTo avoid having the nerve in a constant state of being on, the excess serotonin molecules in the synaptic cleft are eliminated by monoamine oxidase (MAO) enzymes plus a process called catechol-O-methyl transferase (COMT). Some of the remaining serotonin does return to the presynaptic cell in a process of absorption called reuptake. As the serotonin level reduces, the nerve signal is turned off and the system resets to baseline. The communication system is now ready to receive another signal or action potential. The classes of antidepressants that block the reuptake process, leading to increased serotonin, are called SSRIs or selective serotonin reuptake inhibitors. They include drugs called Lexapro, Prozac, Paxil, and Zoloft.

Neurotransmitters 101

The body’s main neurotransmitters are:

  • Dopamine (DA) acts as precursor to norepinephrine and adrenaline
  • Norepinephrine (NE) the workhorse NT for the sympathetic nervous system
  • Adrenaline (A) the NT for the sympathomedullary nervous system
  • Acetylcholine (ACh) the NT for the parasympathetic nervous system
  • Serotonin (5-HT) the body’s feel good NT

We now study each of these in more detail, starting with a group called catecholamines. Catecholamines are a grouping of NTs, which are very often referred to as the stress hormones. They are all derived from tyrosine, an amino acid. These neurotransmitters have the ability to act faster than cortisol, a hormone that responds to stress. The key catecholamines are dopamine, norepinephrine, and adrenaline.

Dopamine is a vital neurotransmitter as well as a precursor to norepinephrine. Dopamine released in the brain acts as a natural reward for pleasurable experiences like when having sex or dining on a delicious meal. It can also be released in response to neutral stimuli and as a result, pleasure becomes associated with those stimuli.

When dopamine is released in excess amounts in the brain, the effects can be anxiety, hyperactivity, and paranoia.

When dopamine levels are low, the effects can be addiction, cravings, compulsive behavior, depression, and inability to concentrate or focus.

Norepinephrine (NE) is an important neurotransmitter that helps to regulate attention and arousal, and plays a part in the fight-or-flight response. It acts both as a neurotransmitter and a hormone. In the brain, it functions as an excitatory NT, putting the body in a state of mental alert. It is produced and acts in the brain to prepare the individual to deal with a perceived threat. It also travels outside the brain. Once outside, it acts as a hormone and plays an important role in increasing heart rate and blood pressure, dilating eye pupils, dilating air passages in lungs, and narrowing blood vessels. It is the main controller that facilitates the actions required for day-to-day stress that we take for granted, such as standing up quickly without feeling dizzy from a reclining position.

If someone is living under ongoing stressful conditions, a long-term excess of norepinephrine in the brain can result. Such is the case of Adrenal Fatigue Syndrome, especially in the moderate to advanced stages. Chronic excess of norepinephrine is called sympathetic overtone. It can cause cellular and tissue inflammation, higher blood pressure, symptoms of hyperthyroidism, and panic attacks.

Chemical Imbalance of NorepinephrineOn the other side of the spectrum, if there is a deficiency of norepinephrine over a long period it may cause behavioral problems, immunological chemical imbalance, impaired cognitive functioning, or secondary hypothyroidism.

Adrenaline (A), also called epinephrine, plays the key role in the urgent fight-or-flight reaction that takes place physiologically in the body in response to an immediate threat when survival is perceived to be at risk. It is the chemical daughter of norepinephrine. Their actions are similar, but adrenaline is much more potent. This hormone is secreted in the adrenal glands under the direction of the HPA axis and produces a rapid rise in blood pressure, rapid heartbeat, and stimulates the release of glucose in the liver. This is the hormone of last resort as far as the body is concern when it is under imminent danger. The more danger the body is perceived to be in, the more adrenaline will be released. Those who are in very advanced stages of AFS are invariably flooded with adrenaline internally. Symptoms include heart palpitations, dizziness on standing, and panic attacks.

Acetylcholine (ACh) is a major neurotransmitter for the parasympathetic nervous system (PNS) and helps the body carry out the day to day housekeeping functions for stimulation of rest-and-digest or feed-an-breed activities that occur when the body is at rest, especially after eating, including urination, sexual arousal, bowel movements, and digestion.

Serotonin is a monoamine neurotransmitter synthesized in specific neurons in the brain, central nervous system and in enterochromaffin cells located in the gastrointestinal tract. It is also called the feel good NT. Inside the brain, the pineal gland is the center for serotonin production. Throughout the entire central nervous system, serotonin has a vital role as an effective neurotransmitter in modulating a number of different areas:

  • Anger
  • Aggression
  • Appetite
  • Body temperature
  • Erection and ejaculation
  • Mood
  • Sexuality
  • Sleep
  • Stimulation of vomiting

Serotonin is also a precursor to melatonin. Once they have completed their task a reuptake or reabsorption of the hormone takes place. Serotonin is effective in making us feel calm and basically good naturally. It helps the mind to relax so that we can easily fall asleep and stay soundly asleep.

Serotonin and melatonin are produced in the body from tryptophan, an amino acid. As we have already discussed, a person who doesn’t have any serotonin cannot produce abundant amounts of melatonin. The ability to convert from one type to another depends on a variety of nutritional cofactors and coenzymes.

For a person to feel well, the overall serotonin level cannot be too high or too low. There should be no chemical imbalance. Chronic excess of serotonin over a long period of time may result in:

  • Behavioral problems
  • Cardiovascular problems
  • Hormonal and immunological imbalances

A long-term depletion or deficiency in serotonin can cause:

  • Depression
  • Gastrointestinal problems
  • Hormonal imbalances
  • Imbalances in the immune system
  • Inflammation
  • Insomnia due to low melatonin
  • Onset of various medical conditions

Neurotransmitter Precursors

Chemical Imbalance and DepressionThe compounds utilized in the manufacturing of neurotransmitters are called precursors. Anything affecting the precursors will in turn affect the resulting NTs and influence how the nervous system functions in the end. If a precursor has a deficiency in a certain aspect, then that can cause a bottleneck or delay in the creation of a particular NT and affect its ultimate functionality. It is also true that if there is an excess of a certain precursor that can cause the resulting NT to have excessively high levels.

  • Precursors of dopamine (DA), norepinephrine (NE) and adrenaline (A):
    DOPA, phenylalanine, tyrosine
  • Precursors of serotonin (5-HT): 5-HTP, tryptophan
  • Precursors of acetylcholine (ACh): phosphatidylcholine, acetyl group amino acids such as N-acetyl-L-cysteine (NAC) or acetyl-L-carnitine (ACL)


There are a number of different neuroactive substances working to promote the proper functioning of the neurotransmitter. The following are some and their contributions:

  • Ascorbic acid (vitamin C)—an anti-oxidant
  • Histamine—mediates allergic and pain reactions, also acts as a potent vasodilator
  • L-Aspartic acid—an excitatory amino acid
  • L-Glutamic acid—an excitatory amino acid
  • L-Lysine—works to prevent extracellular matrix destruction

Neurotransmitter precursors and modulators serve important functions. They are generally less potent and thus available as over the counter nutritional supplements. Their gentle character lends well when used in cases where medications such as NT repletion tools are not indicated or well tolerated, for example. They are also less addictive because they tend to be weaker in action.

Inhibitory vs. Excitatory Neurotransmitters

NTs generally fall into two groups when classified by their actions:

  • Inhibitory NT—Serotonin, glycine, and GABA fall into this category. When we have plenty of these in our system we feel good. These NTs also assist with our sleep and contribute to our sense of self-esteem. When these become depleted in our system we can become angry, depressed and suffer from insomnia.
  • Excitatory NT—These neurotransmitters keep us focused, alert, motivated, and help our memory. They include catecholamines (dopamine, adrenaline, and norepinephrine), and glutamate. A chemical imbalance or a low level of dopamine causes impaired short-term memory, a low sex drive, difficulty with numbers and general fatigue. A chemical imbalance or shortage of norepinephrine will bring on depression, a lack of motivation and ambition, and an increased likelihood of becoming dependent on caffeine and other stimulants. If we have too much norepinephrine then we can arouse panic and have difficulty sleeping. Many street drugs work by stimulating this pathway.

For the body to be in optimum health, NTs of opposing actions need to be perfectly balanced.

L-Glutamate (glutamic acid) is the most vital excitatory neurotransmitter functioning in the brain. It performs a significant role in brain chemistry. It is released by a variety of neurons and acts to stimulate other neurons during synapses. The more glutamate, the higher the levels of excitation will be. Proper rest and sleep are important factors to recover from Adrenal Fatigue and keep a chemical imbalance from happeningIf the excitatory neurotransmitters reach excessively high levels, a state of excitotoxicity exists. This is when the neuronal activation has reached such a high level that the stimulated firing of neurons has become neurologically damaging. Many of the illicit or prescription drugs that abusers take affect either one or both neurotransmitters and cause stimulating or tranquilizing effects on the brain.

On the other end of the spectrum, molecules such as GABA and taurine are part of the inhibitory NTs. GABA is derived from glutamine and synthesized when the active form of vitamin B6 (P5P) is present. Inhibitory NTs inhibit or prevent the firing of neurons. It plays a critical role in the regulation of neuronal excitability throughout the entire nervous system so that the body does not operate in a continuous state of high or excitment. They reduce anxiety and promote calmness.

Read Part 2 | Part 3 | Part 4 | Part 5 | Part 6

© Copyright 2015 Michael Lam, M.D. All Rights Reserved.

Dr. Lam’s Key Questions

That is an interesting question. Normal, the body self-adjusts. However, in severe cases, the thyroid function could be permanently affected. In such case, during and even after anorexia is resolved, there are residual problems with thyroid that can remain for a long time.

The cortisol produce by the adrenal glands is anti-inflammatory. When the adrenals are fatigued, cortisol production goes down, and your body becomes more sensitive and sensitivities to food, chemicals will start surfacing.

Modern medicine is controlled by the pharmaceutical companies, where the big bucks are. Using food to improve health does not generate the money.

Chemical Imbalance
5 - "Dear Health Coaches:"
Dear Health Coaches:

First of all, I just wanted to say THANK YOU for taking me on as a client. I can't tell you how comforting it is to actually be able to work with people who are so knowledgeable about this complex condition. It has been such a confusing and scary journey over the past 20 years.

I am very sensitive to any change going on in my body - good or bad - so I always have to go very slow when starting anything new or making any changes From reading all the info in the books and on the site, I can tell you have worked with people like me before (and some who are probably much worse) so it's comforting to know you understand my sensitivity and that I will have to go really slowly. Other doctors in the past have just thought I was being a hypochondriac and not believed me or tried to rush me through protocols and just made my situation much worse.

Thanks so much for your time.